PHOL0002

• Resting potential:

  • skeletal muscle = -90 mV
  • astroglia = -80 to -90 mV
  • neurons = -60 to -70 mV
  • smooth muscle = -60 mV
  • photoreceptors = -40 mV
  • erythrocytes = -9 mV
• Resting membrane potential is mainly determined by the potassium gradient across the plasma membrane
• Sodium pump activity leads to the accumulation of K+ in the cellSome of these K+ leak out of cells via potassium channels Na+ unable to replace lost K+ Therefore there is a build up of negative charge in the cell (as K+ is lost) that can be detected as a potential difference
• Ligand gated channels open in response to specific chemical signals, e.g. nicotinic acetylcholine receptor
• Voltage gated channels open in response to changes in the membrane potential, e.g. sodium and potassium channels in neuron axon
• Cells communicate by:

  • diffusible chemical signals
  • direct surface contact between adjacent cells
  • direct cytoplasmic contact between adjacent cells via gap junctions
• Cells use chemical signals:

  • for localised signalling (autocrine and paracrine)
  • generalised signalling to sites remote from secretion site (endocrine)
  • as neurotransmitters in synaptic signalling
• autocrine signals affect the secreting cell itself

  paracrine signals affect cells within a relatively small radius
• Hormones = chemical signals secreted by endocrine glands into the blood to act on distant target cells
• Signalling molecules are divided into:

  • esters (acetylcholine)
  • amino acids (glutamic acid)
  • amines (adrenaline)
  • peptides (ADH)
  • proteins (insulin)
  • steroids (testosterone)
  • iodinated amino acids (thyroid hormones)
  • eicosanoids (prostaglandin)
  • inorganic gas (nitric oxide)
  • nucleosides and nucleotides (adenosine)
• Substances that activate a receptor = agonists

  Substances that block the effects of an agonist = antagonist
• Secondary messengers:

  • cAMP - activates protein kinase A which regulates the activity of a large number of enzymes
  • Inositol triphosphate - triggers the release of calcium from intracellular stores
  • Diacylglycerol - regulates the activity of certain enzymes via protein kinase C
• Gap junctions permit the exchange of small molecules and ions between neighbouring cells
• Steroid hormones pass through the plasma membrane and bind to intracellular receptors to regulate gene transcription
• Skeletal muscle is activated by action potentials in the motor nerves - neurogenic contractions
• Cardiac and most smooth muscle have an intrinsic rhythm that is modulated by action potentials in autonomic nerves - myogenic contractions
• Motor unit = the motor neuron, its axon and all the muscle fibres supplied by the axon and its branches
• Contraction cycle:

  1. Myosin heads hydrolyse ATP an become reoriented and energised
  2. Myosin heads bind to actin, forming crossbridges
  3. Myosin crossbridges rotate towards centre of the sarcomere (power stroke)
  4. As myosin heads bind ATP, the crossbridges detach from actin
• Isotonic contractions = changes in length, categorised into:

  • concentric contraction - muscle activation that increases tension on a muscle as it shortens (bicep curl)
  • eccentric contraction - muscle fibres are stretched out
• Isometric contractions - do not cause any joint movement, no lengthening or contraction of muscles
• Amount of force exerted depends on:

  • number of active motor units
  • cross-sectional area of the muscle
  • frequency of stimulation
  • initial resting length of the muscle
  • rate at which the muscle shortens
• Pacemaker activity of the SA node can be modulated by autonomic nerves - chronotropic regulation
• Cardiac action potential coincides with contractile response so cardiac muscle cannot be tetanised
• Two types of smooth muscle:

  • single unit - contractions are mainly myogenic in origin
  • multi unit - contractions are initiated by autonomic nerve fibres and are therefore neurogenic in origin
• Contractile proteins of smooth muscle are arranged in a loose matrix to allow a greater degree of shortening than seen in striated muscle
• Blood consists of:

  • plasma (fluid component) - small solutes, larger molecules
  • cellular component - red blood cells, white blood cells, platelets
• Red blood cells - transport oxygen and carbon dioxide, facilitated by the presence of haemoglobin

  Anaemia = oxygen carrying capacity of the blood is reduced
• Haematocrit ratio = the proportion of blood made up of cells (mainly RBC)

  Determined using centrifugation as red blood cells will be packed at the bottom
• Lower than normal haematocrit:

  • loss of blood
  • nutritional deficiency
  • bone marrow problems
  • abnormal haemoglobin
• Higher than normal haematocrit

  • living at high altitudes
  • chronic smokers
  • dehydration
• Starling's forces = pressures involved in the movement of fluids across capillary membranes
• Starling's equation: the net fluid movements between the compartments depends on:

  • capillary hydrostatic pressure - pressure forcing fluid out of the capillary
  • interstitial hydrostatic pressure - pressure forcing fluid out of the interstitial space
  • capillary oncotic pressure - osmotic pressure forcing fluids to enter the capillary from the interstitial space
  • interstitial oncotic pressure - osmotic pressure forcing fluids to enter interstitial space from the capillary
• Capillary hydrostatic pressure = pressure forcing fluid out of the capillary
• Filtration coefficient = based on how large and leaky the capillary wall is
• Reflection coefficient = when some proteins cross the vessel wall into the interstitium, it reduces the oncotic pressure in the capillary and increases oncotic pressure in the interstitium
• Oedema: when filtration forces exceed absorption forces, an accumulation of extravascular fluid occurs

  Pc > Pi leads to congestive heart failure

  πi > πc leads to liver failure, nephrotic syndrome, extensive tissue trauma
• Haemostasis = the process of stopping blood loss by vasoconstriction, platelet aggregation, blood coagulation
• Vasoconstriction = restricted blood flow due to a contraction of the smooth muscle around the damaged blood vessel due to physical stimulation of the muscle
• Platelet aggregation = damage to a blood vessel causes platelets to bind to the injury site forming a platelet plug, accelerated by platelets which release factors promoting further platelet aggregation
• Coagulation = a sequence of reactions converting the plasma protein fibrinogen into fibrin